Clinical, Sonographic, and Pathological Characteristics of RAS-Positive Versus BRAF-Positive Thyroid Carcinoma

Kakarmath, Sujay; Heller, Howard T.; Alexander, Caroline A; Cibas, Edmund S.; Krane, Jeffrey F.; Barletta, Justine A.; Lindeman, Neal I.; Frates, Mary C.; Benson, Carol B.; Gawande, Atul A.; Cho, Nancy L.; Nehs, Matthew A.; Moore, Francis D.; Marqusee, Ellen; Kim, Mathew I.; Larsen, P. Reed; Kwong, Norra; Angell, Trevor E.; Alexander, Erik K.

doi:10.1210/jc.2016-2620

Cited by 23 publications

(18 citation statements)

References 28 publications

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“…Interestingly, we observed that FNAs with RAS and RAS ‐like mutations were obtained from nodules that were larger than those harboring BRAF V600E and BRAF ‐like alterations—a finding in line with other experiences suggesting that RAS ‐mutated nodules grow at a faster rate …”

Section: Discussionsupporting

confidence: 91%

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7‐gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy

Bellevicine

Migliatico

Sgariglia

et al. 2019

Cancer Cytopathology

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BACKGROUND: Thyroid fine-needle aspiration (FNA) is a reliable and cost-effective diagnostic tool for establishing the nature of thyroid nodules, although up to 30% of FNAs are still classified as "indeterminate." Molecular testing of FNAs could improve preoperative diagnosis, thereby reducing unnecessary surgery. In this multicenter prospective study the authors investigated, using a 7-gene assay, the distribution and diagnostic impact of BRAF, RAS, RET/PTC, and PAX8/ PPARg, the most frequent genomic alterations occurring during thyroid oncogenesis. METHODS: In total, of 1172 routine FNAs from 7 centers in southern Italy were classified according to the Bethesda System for Reporting ThyroidCytopathology. Each specimen was tested, and molecular data were compared with available histology or cytologic follow-up. RESULTS: In particular, for atypia of undetermined significance/follicular lesion of undetermined significance cases, the 7-gene test confirmed the high positive predictive value of BRAFV600E and BRAF-like mutations (80%) and the moderate positive predictive value of RAS-like alterations (32.4%), suggesting different surgical management, depending on the type of mutation. The rate of mutation-positive FNAs was strictly related to the risk of malignancy of each diagnostic class, supporting the identification of prognostically relevant diagnostic categories. CONCLUSIONS:The 7-gene panel test improves the preoperative risk stratification of indeterminate thyroid FNAs, especially when considering the biologic significance of the different types of mutations. Moreover, the rate of mutation-positive FNAs is related to the risk of malignancy of each diagnostic class.

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Section: Discussionsupporting

confidence: 91%

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7‐gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy

Bellevicine

Migliatico

Sgariglia

et al. 2019

Cancer Cytopathology

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“…A recent trial demonstrated that among 60 patients with the BRAF mutation, 90% had LVI. In another study, among 71 BRAF(+) PTC patients, 46% had LVI, and the BRAF mutation was found to be a statistically significant risk factor for LVI in these PTC patients [45]. Our study is the largest clinical series investigating the association between the presence of LVI and BRAF mutation in PTC patients.…”

Section: Discussionmentioning

confidence: 53%

“…The BRAF gene mutation is found in approximately 45% of thyroid cancer patients and most studies indicate that the BRAF mutation is a poor prognostic factor in these patients. However, recent studies on the BRAF mutation status in PTC patients showed conflicting results; furthermore, limited data exist on the association between the BRAF mutation and LVI in PTC patients [44,45]. A recent trial demonstrated that among 60 patients with the BRAF mutation, 90% had LVI.…”

Section: Discussionmentioning

confidence: 99%

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

Sezer

Çelık

Bulbul

et al. 2017

Bosn J of Basic Med Sci

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Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.

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“…MAP kinase, PI3K, and V600E mutation in BRAF oncogene are common features in melanoma and TC [ 52 , 53 ]. On the cellular level, RAS and BRAF mutations, but not ARAF or CRAF mutations, play significant roles in the ERK signaling pathway [ 54 , 55 , 56 ]. For example, ERK accumulates in the nucleus following stimulation by mitogenic signals.…”

Section: Dysregulation Of Nucleocytoplasmic Transport In Melanoma mentioning

confidence: 99%

New Insights into the Link between Melanoma and Thyroid Cancer: Role of Nucleocytoplasmic Trafficking

Zerfaoui

Dokunmu

Toraih

et al. 2021

Cells

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Cancer remains a major public health concern, mainly because of the incompletely understood dynamics of molecular mechanisms for progression and resistance to treatments. The link between melanoma and thyroid cancer (TC) has been noted in numerous patients. Nucleocytoplasmic transport of oncogenes and tumor suppressor proteins is a common mechanism in melanoma and TC that promotes tumorigenesis and tumor aggressiveness. However, this mechanism remains poorly understood. Papillary TC (PTC) patients have a 1.8-fold higher risk for developing cutaneous malignant melanoma than healthy patients. Our group and others showed that patients with melanoma have a 2.15 to 2.3-fold increased risk of being diagnosed with PTC. The BRAF V600E mutation has been reported as a biological marker for aggressiveness and a potential genetic link between malignant melanoma and TC. The main mechanistic factor in the connection between these two cancer types is the alteration of the RAS-RAF-MEK-ERK signaling pathway activation and translocation. The mechanisms of nucleocytoplasmic trafficking associated with RAS, RAF, and Wnt signaling pathways in melanoma and TC are reviewed. In addition, we discuss the roles of tumor suppressor proteins such as p53, p27, forkhead O transcription factors (FOXO), and NF-KB within the nuclear and cytoplasmic cellular compartments and their association with tumor aggressiveness. A meticulous English-language literature analysis was performed using the PubMed Central database. Search parameters included articles published up to 2021 with keyword search terms melanoma and thyroid cancer, BRAF mutation, and nucleocytoplasmic transport in cancer.

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Clinical, Sonographic, and Pathological Characteristics of RAS-Positive Versus BRAF-Positive Thyroid Carcinoma

Cited by 23 publications

References 28 publications

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7‐gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy

Evaluation of BRAF, RAS, RET/PTC, and PAX8/PPARg alterations in different Bethesda diagnostic categories: A multicentric prospective study on the validity of the 7‐gene panel test in 1172 thyroid FNAs deriving from different hospitals in South Italy

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

New Insights into the Link between Melanoma and Thyroid Cancer: Role of Nucleocytoplasmic Trafficking

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